Extrapolating Animal Exposures to Humans

Our multi-scale models of the respiratory system offer unprecedented high-resolution insights into how mouse-, rat-, rabbit-, monkey-, or human-specific anatomy and physiology affects how materials are inhaled, transported throughout the respiratory system, and ultimately taken up by respiratory tissues or enter into systemic blood circulation.

Simulations of airflows through the conducting airways of a human showing the impact of airway narrowing in the larynx (insert)

Model features include:

Imaging-based 4D anatomic (3D structure plus time-dependent changes) features from the external nose or mouth through the lung

Fully transient simulations that can mimic realistic breathing patterns or the influence of altered atmospheres such as the use of medical gases.

These models can also take into account implicit heterogeneities in airway-specific airflows, the impacts of diseases such as asthma and COPD, and changes in respiratory behaviors that contribute to target site dosimetry and eventually response.

With extensive funding from the National Institutes of Health and the Department of Energy, PNNL has developed the 3D imaging and computational infrastructure (hardware and software) that makes the development and validation of individualized 3D models a practical stand-alone alternative or complement to low-resolution, non-specific or empirical approaches used in the past to predict dosimetry in the respiratory system.

Simulations of regional airflows and tissue uptake (flux rates) of the reactive vapor, acrolein, in the airways of a human (top), monkey (middle), and rat (bottom).

Our scientists actively participate in NIH's Multi-Scale Modeling Consortium and serve on numerous elected and appointed positions in scientific associations, National Academies of Science and EPA, boards and committees, editorial boards for scientific journals, and grant peer-review groups. Clients include NIH, EPA, DOE, and private industry.